Safety and Tolerability Study of Voreloxin and Cytarabine Combination in Acute Myeloid Leukemia in Humans

An open-label, Phase 1b/2 study using a dose-escalation design with expansion at the maximum
tolerated dose (MTD) using 2 dosing schedules:

During the Schedule A dose-escalation phase, patients with relapsed or refractory acute
myeloid leukemia (AML) enrolled in cohorts of at least 3 patients to identify the MTD. Begin
with a starting dosing regimen of vosaroxin of 10 mg/m2 on Days 1 and 4 of each cycle in
combination with a 24-hour continuous intravenous (CIV) infusion of cytarabine 400 mg/m2/day
× 5 days. If none of the 3 patients or 1 of 6 patients experience a dose-limiting toxicity
(DLT) at the vosaroxin starting dose, dose-escalate vosaroxin. If 2 of 6 patients experienced
a DLT at the vosaroxin starting dose, reduce the dose of cytarabine to reduced to 200 mg/m2
(only case in which the cytarabine could have been reduced). The vosaroxin dose escalated
following a modified Fibonacci schema.

For Schedule B dose-escalation phase, patients with relapsed or refractory AML enrolled in
cohorts of at least 3 patients to identify the MTD. Begin with a starting dose regimen of
vosaroxin of 70 mg/m2 on Days 1 and 4 in combination with cytarabine as a 2-hour infusion of
1 g/m2/day × 5 days. No reductions of cytarabine allowed in Schedule B. If none of the 3
patients or 1 of 6 patients experienced a DLT in the first cohort of Schedule B, escalate the
dose of vosaroxin. If DLTs occurred in 2 of 6 patients during the starting dose, reduce the
vosaroxin dose to 50 mg/m2.

For both Schedules, the highest dose at which fewer than 2 of 6 patients experienced a DLT
during induction became the MTD and the recommended future dose.

Once the MTD of vosaroxin was determined for Schedule A, first relapse patients were enrolled
in the expansion phase at that dose level to obtain additional safety and efficacy
information. When the MTD of vosaroxin was determined for Schedule B, first relapse patients
and patients with primary refractory disease were enrolled in the expansion phase at that
dose level to characterize the safety and efficacy profile in this population.

KEY INCLUSION CRITERIA

1. Relapsed or refractory AML subtypes defined by WHO, except acute promyelocytic
leukemia. Relapsed/refractory disease may be de novo AML or secondary AML

2. Treated with one to threee induction/reinduction AML regimens, prior induction or
consolidation therapy with cytarabine allowed

3. At least 10% blasts by BM biopsy or aspirate

4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

5. Clinical laboratory values of a) Serum creatinine ≤1.5 mg/dL and calculated or
measured creatinine clearance (CRcl) of ≥50 mL/min, b) Total bilirubin ≤1.5 X upper
limit of normal and c) Aspartate aminotransferase (AST) or alkaline phosphatase ≤2.5 X
ULN.

KEY EXCLUSION CRITERIA

Patients with:

1. Allogenic bone marrow transplant/stem cell transplant

2. Persistent, clinically significant, chronic toxicities from prior AML therapy that
would contraindicate the patient's participation in the clinical study due to safety
concerns or compliance with study procedures

3. Acute promyelocytic leukemia

4. Disseminated intravascular coagulation

5. Active infections, unless adequately treated with antibiotic, antiviral, or antifungal
agents within in 7 days before Induction Day 1

6. Active central nervous system involvement by AML

7. Other active malignancies or other malignancies within the last 12 months except
nonmelanoma skin cancer or cervical intraepithelial neoplasia

8. A requirement for hemodialysis or peritoneal dialysis

9. A history of myocardial infarction within the 3 months before treatment with vosaroxin

10. A history of cerebrovascular accident/transient ischemic attack within the 3 months
before treatment with vosaroxin

11. A thromboembolic event (deep vein thrombosis or pulmonary embolus) within 28 days
before treatment with vosaroxin

12. Investigational products taken within 28 days before treatment with vosaroxin, and
non-investigational cancer therapies or radiation therapy within 14 days before
treatment with vosaroxin, with the exception of hydroxyurea.

13. A known intolerance to cytarabine or known allergy to D-sorbitol or methanesulfonic
acid (excipients used in vosaroxin)

14. Prior exposure to vosaroxin

15. Any other medical, psychological, or social condition that contraindicates their
participation in the clinical study due to safety concerns or compliance with study
procedures in the opinion of the Investigator,or Sunesis Medical Monitor

In addition:

16. Women who are pregnant or breastfeeding

17. Women who are of childbearing potential or male patients who had partners of
childbearing potential who were unwilling to use an approved, effective means of
contraception according to the study site's standards